Poster Presentation

Poster A in Poster Session A: Tuesday, August 4, 9:30 – 11:15 am, Kimmel Center, Shorin & Rosenthal Rooms

Neural attractor dynamics predict relapse after rapid pharamacological perturbation of mood in difficult-to-treat depression

Selena Singh¹, Vanessa Pardo Nunez¹, Dario Brooks¹, Ankana Boruah¹, Jasmyn Cunningham¹, Ryan Fitzpatrick¹, Megi Nallbani¹, Warren Fieldus¹, Samuel Campbell¹, Karim Mukhida¹, Jared Allman¹, Tomas Hajek¹, Claire O'Donovan¹, Ahmed Saleh¹, Martin Alda¹, Rudolf Uher¹, Matthew McAdam¹, Abraham Nunes¹; ¹Dalhousie University

Presenter: Selena Singh

Over half of individuals with major depressive disorder develop difficult-to-treat depression (DTD). Although subanaesthetic ketamine produces rapid antidepressant effects, relapse is common; predicting relapse may enable timely intervention. We propose that depression arises from a pathologically stable neural attractor state. Here, ketamine acts as a controlled perturbation that destabilizes this attractor; we hypothesized that larger perturbations may yield more durable antidepressant responses. In a randomized, double-blind, cross-over pilot study, adults with DTD (N=22) received single doses of intravenous ketamine and midazolam. Resting-state EEG, depression and anhedonia measures were collected. We applied recurrence quantification analysis to source-localized EEG to measure changes in dynamical features indexing attractor stability. Exponential curves were numerically fitted to depression scores post-infusion, placing individuals along a continuum from deterministic to stochastic relapse patterns. Greater post-infusion neural destabilization predicted lower depression severity two weeks later only in individuals with a deterministic relapse trajectory. Furthermore, post-infusion improvements in anhedonia predicted both deterministic relapse trajectory and associated neural de-stabilization. Together, these findings support a dynamical systems account of DTD while highlighting neural attractor de-stabilization as a potential biomarker of antidepressant durability in "endogenous" forms of depression.

Topic Area: Development, Individual Differences & Clinical Populations